Tadros Sherif F, D'Souza Mary, Zhu Xiaoxia, Frisina Robert D
International Center for Hearing & Speech Research, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, New York, United States of America ; Otolaryngology Dept., University of Rochester Medical School, Rochester, New York, United States of America.
International Center for Hearing & Speech Research, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, New York, United States of America ; Otolaryngology Dept., University of Rochester Medical School, Rochester, New York, United States of America ; Depts. Chemical & Biomedical Engineering, Communication Sciences & Disorders, and Global Center for Hearing & Speech Research, University of South Florida, Tampa, Florida, United States of America.
PLoS One. 2014 Feb 28;9(2):e90279. doi: 10.1371/journal.pone.0090279. eCollection 2014.
Age-related hearing loss - presbycusis - is the number one neurodegenerative disorder and top communication deficit of our aged population. Like many aging disorders of the nervous system, damage from free radicals linked to production of reactive oxygen and/or nitrogen species (ROS and RNS, respectively) may play key roles in disease progression. The efficacy of the antioxidant systems, e.g., glutathione and thioredoxin, is an important factor in pathophysiology of the aging nervous system. In this investigation, relations between the expression of antioxidant-related genes in the auditory portion of the inner ear - cochlea, and age-related hearing loss was explored for CBA/CaJ mice. Forty mice were classified into four groups according to age and degree of hearing loss. Cochlear mRNA samples were collected and cDNA generated. Using Affymetrix® GeneChip, the expressions of 56 antioxidant-related gene probes were analyzed to estimate the differences in gene expression between the four subject groups. The expression of Glutathione peroxidase 6, Gpx6; Thioredoxin reductase 1, Txnrd1; Isocitrate dehydrogenase 1, Idh1; and Heat shock protein 1, Hspb1; were significantly different, or showed large fold-change differences between subject groups. The Gpx6, Txnrd1 and Hspb1 gene expression changes were validated using qPCR. The Gpx6 gene was upregulated while the Txnrd1 gene was downregulated with age/hearing loss. The Hspb1 gene was found to be downregulated in middle-aged animals as well as those with mild presbycusis, whereas it was upregulated in those with severe presbycusis. These results facilitate development of future interventions to predict, prevent or slow down the progression of presbycusis.
年龄相关性听力损失——老年性聋——是头号神经退行性疾病,也是老年人群最主要的沟通障碍。与许多神经系统的衰老性疾病一样,与活性氧和/或氮化物(分别为ROS和RNS)产生相关的自由基损伤可能在疾病进展中起关键作用。抗氧化系统(如谷胱甘肽和硫氧还蛋白)的功效是衰老神经系统病理生理学中的一个重要因素。在本研究中,针对CBA/CaJ小鼠探索了内耳听觉部分——耳蜗中抗氧化相关基因的表达与年龄相关性听力损失之间的关系。40只小鼠根据年龄和听力损失程度分为四组。收集耳蜗mRNA样本并生成cDNA。使用Affymetrix®基因芯片分析56个抗氧化相关基因探针的表达,以评估四个受试组之间基因表达的差异。谷胱甘肽过氧化物酶6(Gpx6)、硫氧还蛋白还原酶1(Txnrd1)、异柠檬酸脱氢酶1(Idh1)和热休克蛋白1(Hspb1)的表达在受试组之间存在显著差异,或显示出较大的倍数变化差异。使用qPCR验证了Gpx6、Txnrd1和Hspb1基因表达的变化。随着年龄/听力损失,Gpx6基因上调,而Txnrd1基因下调。发现Hspb1基因在中年动物以及轻度老年性聋动物中下调,而在重度老年性聋动物中上调。这些结果有助于未来开发预测、预防或减缓老年性聋进展的干预措施。